An in vitro culture system was used to screen compounds for antimicrosporidial activities. Compounds that inhibited microsporidial growth by more than 50% at non-toxic doses, in vitro included, a) the benzimidazoles; albendazole, mebendazole and thiabendazole, b) the chitin synthesis inhibitors; lufenuron and tunicamycin, c) two angiogenesis inhibitors; fumagillin and TNP-470, c) four of ten dicationic compounds that were supplied by Drs. J. Ed Hall and R. Tidwell, d) 13 of 61 purine and deazapteridine deriviatives synthesized at Southern Research Institute, and e) four "miscellaneous" compounds; berberine, sodium nitroprusside, desacetylnitazoxanide, and nitazoxanide. To date, however, the most effective compounds tested in vitro continue to be albendazole, fumagillin, and TNP-470. Studies also were conducted to fractionate the different stages of microsporidia to eventually generate cDNA libraries that can be used to define and characterize targets of lead compounds. To date, mature spores, sporoblasts, and empty spore husks have been separated using Percoll sedimentation. Meront (early proliferative stages) have not yet been enriched, but studies are continuing toward that goal.